The American Institute of Nutrition (AIN), the professional society of U.S. nutrition research scientists, hereby applies for funds to support travel for young scientists from the Americas (who are judged as outstandingly qualified scientists) to participate in the XV International Congress of Nutrition to be held in Adelaide, Australia, September 26- October 1, 1992. At the international level this congress is sponsored by the International Union of Nutritional Sciences (IUNS), a member of the International Council of Scientific Unions, which has adhering bodies in 64 countries. The U.S. adhering body, with which the AIN closely coordinates associated activities, is the U.S. National Committee for IUNS, National Research Council, Commission on Life Sciences, Washington, D.C., 20418. Since 1946, IUNS has sponsored this meeting in 13 countries (the last, in Seoul, Korea, in 1989). The Congress provides an international forum for the exchange of scientific knowledge in nutrition, which is receiving increasing global recognition as a significant component of public health and of social and economic development. The U.S. nutrition research community, represented by AlN and its division, the American Society for Clinical Nutrition (ASCN), is the scientific leader in nutrition research relevant to world problems including relationships of diet and chronic disease as well as consequences of nutrient deficiencies. Its members will make major contributions (see Attachment F) to this Congress which will provide a unique opportunity for communication with nutrition scientists active in the pacific region. The Australian Scientific committee has planned 10 themes, including 48 symposia, 5 plenary lectures, 36 workshops and numerous poster and satellite sessions. The Congress theme, "Nutrition in a Sustainable Environment," will focus on nutrition and the environment; nutrition policies and programs; prevention of chronic disease; molecular biology of essential nutrients; nutrition and performance. This request for $50,000 will be matched by up to $50,000 from the AIN. The availability of the grants will be widely announced, and awards will be apportioned by a committee on a competitive basis to U.S. and to a limited number of other Western Hemisphere scientists. Preference will be given to scientists in the early stages of their careers and limited to applicants making substantive contributions to the success of the Congress through research communication. Support of this grant request by U.S. Federal funding agencies will be widely publicized and would be consistent with the importance of nutrition recognized by the U.S. Public Health Service (PHS) and the Department of Health and Human Services (DHHS) in the planning of the International Conference on Nutrition scheduled for December, 1992 in Rome, Italy.GRANT=K11DK02210 The liver plays a crucial role in the immune response to injury and infection as the main site of clearance for endotoxin and the key producer of acute phase proteins and cytokines [6,103,104]. Lipopolysaccharide binding protein(LBP), a recently described acute phase protein, is the key component of a novel pathway in which endotoxin or more specifically lipopolysaccharide(LPS) triggers the production of cytokines. LBP forms a high affinity complex with the lipid A portion of LPS and together this complex binds to the monocytic differentiation antigen CD14 to upregulated tumor necrosis factor-alpha (TNF) production by 100- to 1000-fold[53,72]. Most of the endotoxic effects of LPS can be mediated by TNF[105] and overproduction of TNF has been implicated in the pathogenesis of septic shock and multiorgan failure[105,106]. Little is known about the factors which regulate of hepatic LBP production. The cDNA clones of LBP have been isolated from human and rabbit acute phase livers[53]; however, these models have been difficult to use for the study of hepatic LBP production. We have thus proceeded to clone the cDNA for LBP in the rat. Preliminary results from our laboratory using a partial cDNA clone for rat LBP shows the upregulation of LBP steady state mRNA levels in the acute phase response. Early results show that this upregulation may be mediated through IL-6 in a fashion similar to other acute phase proteins. Delineation of the signals which regulate LBP expression both at the cellular and genetic level is critical to the understanding of how the liver responds to infection and injury. In the physiologic state, LBP likely serves as a sentinel to augment the host response to LPS. However, during pathologic states such as overwhelming sepsis and multiple organ failure, LBP may amplify or maintain the detrimental overproduction of cytokines which lead to organ dysfunction and death. An understanding of mechanisms which regulate LBP production will point out therapeutic modalities with which to modify pathologic responses. The aims of this proposal are therefore intimately related: l) to clone, purify, and express rat LBP and generate specific antibodies for use in studying the regulation of LBP production, 2) to delineate the signals which regulate hepatic LBP production.